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Examination of Zinc, S-adenosylmethionine, and Combination Therapy Versus Placebo in Alcoholics (ExZACTO)

This study is currently recruiting participants.
Verified November 2013 by Emory University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Ashish Mehta, MD, MSc, Atlanta VA Medical Center
ClinicalTrials.gov Identifier:
NCT01899521
First received: June 27, 2013
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

This is a randomized, placebo controlled trial of dietary zinc and S-adenosylmethionine (SAMe) in otherwise healthy alcoholic US veterans. The primary goal is to determine if either dietary zinc or S-adenosylmethionine (SAMe) can augment lung immune defenses in alcoholics and thereby decrease the risk of lung injury and infection.


Condition Intervention
Alcoholism
Procedure: Bronchoscopy
Dietary Supplement: Zinc sulfate 220 mg once daily
Dietary Supplement: S-adenosylmethionine 400 mg twice daily

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Examination of Zinc, S-adenosylmethionine, and Combination Therapy Versus Placebo in Otherwise Healthy Alcoholic Patients and Its Effect on the Alcoholic Lung Phenotype

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Primary Endpoint [ Time Frame: Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) ] [ Designated as safety issue: No ]
    Improvement in alveolar macrophage phagocytic index. Phagocytic index will be measured before and after treatment phase. Phagocytic index is calculated using isolated alveolar macrophages from the bronchoscopy procedure such that phagocytic index = (total number of engulfed cells/total number of counted macrophages) × (number of macrophages containing engulfed cells/total number of counted macrophages) × 100.


Secondary Outcome Measures:
  • Secondary Endpoint [ Time Frame: Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) ] [ Designated as safety issue: No ]
    Improvement in alveolar macrophage intracellular zinc. Intracellular zinc will be measured before and after treatment phase using isolated alveolar macrophages. The units of measure are relative fluorescence units/cell (RFU/cell) and measured using confocal microscopy techniques.


Other Outcome Measures:
  • Secondary endpoint [ Time Frame: Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) ] [ Designated as safety issue: No ]
    Improvement in redox potential in the alveolar space. Redox potential will be measured before and after treatment phase using lavage fluid and blood plasma.

  • Secondary endpoint [ Time Frame: Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) ] [ Designated as safety issue: No ]
    Improvement in alveolar macrophage granulocyte macrophage - colony stimulating factor (GM-CSF) receptor expression. GM-CSF receptor expression will be measured before and after treatment phase using isolated alveolar macrophages. The units of measure are relative fluorescence units/cell (RFU/cell) and measured using confocal microscopy techniques. Both alpha- and beta-subunits of the receptor will be measured.

  • Secondary endpoint [ Time Frame: Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) ] [ Designated as safety issue: No ]
    Improvement in serum zinc level. Serum zinc will be measured before and after treatment phase by collecting blood plasma. The units of measure are mg/dl.


Estimated Enrollment: 100
Study Start Date: May 2013
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo zinc and placebo SAMe
Placebo tablet of zinc sulfate once daily and placebo tablet of s-adenosylmethionine twice daily
Procedure: Bronchoscopy
Involves flexible fiberoptic bronchoscopy with standardized bronchoalveolar lavage (BAL) technique (isotonic saline in a sub-segment of the right middle lobe or lingula) using standard conscious sedation techniques.
Active Comparator: Active zinc and placebo SAMe
Zinc sulfate 220 mg once daily and placebo tablet of s-adenosylmethionine twice daily
Procedure: Bronchoscopy
Involves flexible fiberoptic bronchoscopy with standardized bronchoalveolar lavage (BAL) technique (isotonic saline in a sub-segment of the right middle lobe or lingula) using standard conscious sedation techniques.
Dietary Supplement: Zinc sulfate 220 mg once daily
Active Comparator: Placebo zinc and active SAMe
Placebo tablet of zinc sulfate once daily and s-adenosylmethionine 400 mg twice daily
Procedure: Bronchoscopy
Involves flexible fiberoptic bronchoscopy with standardized bronchoalveolar lavage (BAL) technique (isotonic saline in a sub-segment of the right middle lobe or lingula) using standard conscious sedation techniques.
Dietary Supplement: S-adenosylmethionine 400 mg twice daily
Other Name: SAMe
Active Comparator: Active zinc and active SAMe
Zinc sulfate 220 mg once daily and s-adenosylmethionine 400 mg twice daily
Procedure: Bronchoscopy
Involves flexible fiberoptic bronchoscopy with standardized bronchoalveolar lavage (BAL) technique (isotonic saline in a sub-segment of the right middle lobe or lingula) using standard conscious sedation techniques.
Dietary Supplement: Zinc sulfate 220 mg once daily Dietary Supplement: S-adenosylmethionine 400 mg twice daily
Other Name: SAMe

Detailed Description:

Alcohol abuse is a major burden on society and even more of a problem in the veteran population. Chronic alcohol ingestion can have serious health consequences including pneumonia and acute lung injury, which can occur suddenly and without warning even in physically fit individuals without apparent signs of alcohol dependence. Therefore, it is vital for the health of our veterans and indeed our entire population to identify effective treatments that can limit or even prevent these devastating consequences. The primary goal of this clinical research project is to determine if dietary zinc or supplements of the antioxidant S-adenosylmethionine (SAMe) can augment lung immune defenses in otherwise healthy alcoholics and thereby decrease the risk of lung injury and infection. There is already strong evidence from our experimental animal model that moderate daily alcohol ingestion for as little as six weeks causes oxidative stress and zinc deficiency in the lung. These derangements result insult in dysfunction of the alveolar macrophage, which is the resident immune cell, and predisposes animals to the development of pneumonia. Importantly, in this same animal model, we found that adding either zinc or antioxidants to the diet prevents these problems and preserves lung health even during daily alcohol ingestion.

This project will translate basic findings in the animal model to the clinical setting and determine whether or not zinc or SAMe supplements are effective in humans who pathologically consume alcohol. This project will enroll veterans seen at the Atlanta Veterans Hospital in the Substance Abuse Treatment Program (SATP). Participants will be evaluated by undergoing a procedure to obtain samples of fluid from their lungs, measure zinc levels, redox potential, and assess how well their alveolar macrophages respond to bacteria (by determining phagocytic capacity). After completion of the initial evaluation, the participants will be randomized to receive standard treatment (placebo), zinc supplements, dietary SAMe, or the combination of zinc and SAMe for 14 days. All subjects will be evaluated for two weeks as they undergo treatment. At the end of this two week period, measurements of lung zinc, redox potential and macrophage function will be repeated and compared between the two groups. The hypothesis is that both dietary zinc and SAM supplements will improve the immune function of the alveolar macrophage.

If this project is successful, it will lead to larger clinical trials to determine if either dietary zinc and/or SAMe supplements can be effective even in the acute clinical setting and improve outcomes in alcoholics who develop pneumonia or acute lung injury. Overall, both zinc and SAMe supplements are safe and inexpensive to provide, allowing these potential treatments to be easily implemented in the veteran population as well as society in general. Given the significant burden of unhealthy alcohol use, we need ways to limit the physical consequences of alcohol abuse while we continue the efforts at public education and addiction treatment.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-55 years
  • Active alcohol use disorder

Exclusion Criteria:

  • Any active and uncontrolled medical problem(s)
  • Known zinc deficiency
  • Primary substance of abuse something other than alcohol
  • Current abnormal chest x-ray
  • HIV-positive
  • Any disorder of blood coagulation
  • Currently on medical treatment with anti-coagulants (including warfarin, heparin, direct thrombin inhibitors, or anti-platelet agents)
  • Daily use of non-steroidal anti-inflammatory agents (with the exception of patients taking only daily aspirin 81 mg)
  • Daily use of vitamins or other nutritional supplements
  • Renal impairment (GFR < 60)
  • Active bipolar disorder
  • Active Parkinson's disease
  • Current pregnancy
  • Contraindication to treatment with zinc or S-adenosylmethionine
  • Inability to give informed consent (i.e., limited cognitive capacity)
  • Non-English speaking
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01899521

Contacts
Contact: Ashish J Mehta, MD 404-321-6111 ext 2086 ashish.mehta@va.gov

Locations
United States, Georgia
Atlanta VA Medical Center Recruiting
Decatur, Georgia, United States, 30033
Contact: Amy L Anderson, BSN    404-321-6111 ext 3137    amy.anderson2@va.gov   
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Ashish J Mehta, MD Emory University
  More Information

No publications provided

Responsible Party: Ashish Mehta, MD, MSc, Assistant Professor of Medicine, Emory University, Atlanta VA Medical Center
ClinicalTrials.gov Identifier: NCT01899521     History of Changes
Other Study ID Numbers: IRB00060773, 1IK2CX000643
Study First Received: June 27, 2013
Last Updated: November 22, 2013
Health Authority: United States: Department of Veterans Affairs
United States: Emory University Institutional Review Board
United States: Research and Development Committee, Atlanta VAMC

Keywords provided by Emory University:
alcoholism
lung health
pulmonary
macrophage
zinc
SAMe
S-adenosylmethionine
alveolar

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Zinc
Zinc Sulfate
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Astringents
Dermatologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014